Partners: Teaming up for Breakthroughs

Pfizer’s Hospital medicines reach patients at virtually every stage of life. The depth and breadth of our portfolio of trusted medicines and capabilities, and our presence in 160 countries, enables us to deliver value to patients throughout the world.

We are proud to provide access to our quality medicines to healthcare systems and patients in both developing and emerging markets. Pfizer’s Hospital medicines currently offers one of the industry’s largest and most diverse portfolios of anti-infectives and we’re a leader in sterile injectable manufacturing worldwide including the emerging markets.

Strategic Areas of Interest

Pfizer’s Hospital medicines reach patients at virtually every stage of life. The depth and breadth of our portfolio of trusted medicines and capabilities, and our presence in 160 countries, enables us to deliver value to patients throughout the world.

We are proud to provide access to our quality medicines to healthcare systems and patients in both developing and emerging markets. Pfizer’s Hospital medicines currently offers one of the industry’s largest and most diverse portfolios of anti-infectives and we’re a leader in sterile injectable manufacturing worldwide including the emerging markets.

Pfizer is a global leader in discovering and developing medicines for patients suffering from chronic immune diseases. Pfizer is committed to the discovery and development of novel therapeutics to help patients living with immune-inflammatory diseases. Pfizer Inflammation & Immunology is focused on discovering and developing the next generation of therapies for immune- mediated diseases. Pfizer is interested in entering into strategic relationships with innovative collaborators to develop novel and differentiated therapies for autoimmune diseases.

We are interested in establishing alliances to develop therapeutics, expand disease biology understanding, and identify biomarkers that impact three main areas:

• Rheumatology
  • Rheumatoid Arthritis
  • Systemic / Cutaneous Lupus Erythematosus
  • Lupus Nephritis
  • Scleroderma, localized and systemic
  • Systemic Sclerosis
  • Myositis
  • Sjögren's Syndrome
  • Vasculitis
  • Giant Cell Arteritis
  • Rare rheumatologic diseases
  • Spondyloarthropathies
• Gastroenterology/Hepatology
  • Inflammatory Bowel Disease
  • F4 Non-Alcoholic Steatohepatitis
  • Fibrosing / Stricturing Crohn’s Disease
  • Autoimmune Hepatitis
  • Refractory Celiac
  • Eosinophilic Esophagitis
  • Systemic aspects of food allergy
• Medical Dermatology
  • Atopic Dermatitis
  • Alopecia Areata
  • Vitiligo
  • Hidradenitis Suppurativa
  • Chronic Spontaneous Urticaria
  • Pruritis indications: Lichen Sclerosus, Seborrheic / Perioral Dermatitis, Chronic Hand Eczema, Prurigo Nodularis
  • Bullous Pemphigoid,
  • Pemphigus Vulgaris
• Non-GI/Hepatology Fibrotic Diseases
• Other indications with high unmet need that are related to those above

Specific areas of interest include:

• Cytokines and their signaling pathways
• Adaptive Immunity, Lymphocyte biology including Th17 lymphocytes
• Regulatory cells and Tolerance induction
• Host-microbial interactions and microbiome with an interest in epithelial barrier
• Leukocyte metabolism
• Innate Immunity and Innate Lymphoid Cell biology
• Oxidative stress modulators
• Pan anti-fibrotics
• Novel methods to target pathogenic inflammatory fibroblast populations
• Technology platforms and products to help understand patient segmentation in the disease areas of interest and develop precision medicine strategies for innovative portfolio products
• Technology platforms and products that allow for greater tissue and cell specific delivery

Not actively seeking partnering opportunities in:

• TNFα, IL-1ß targeting biologics
• B cell depleting biologics
• Corticosteroids

Cardiovascular diseases (CVD) remain the leading cause of global mortality, accounting for one in every two adult deaths worldwide. The rates of CVD-related morbidity, including heart-failure, peripheral arterial disease and nephropathy are increasing as more patients survive hearts attacks, and the population ages. In addition, Metabolic Diseases, specifically Type 2 diabetes (T2D) and obesity, are major health problems that have reached epidemic proportions worldwide. Globally T2D and obesity incidence have more than doubled in the past two decades. Importantly, CVD and T2D impose large economic burdens on the individual patient and on national healthcare systems and economies. Pfizer scientists are eager to work with world-class partners who share our mission to develop novel and differentiated medicines to improve the lives of patients suffering from CVD.

Pfizer is interested in partnering to develop therapeutics, expand our understanding of disease biology, and identify biomarkers that can help us impact:

• CVD (Heart failure, hypertriglyceridemia, atherosclerosis)
• Type 2 diabetes and related disorders such as hyperinsulinemia
• Non-alcoholic fatty liver disease (NAFLD), Non-alcoholic steatohepatitis (NASH), and liver cirrhosis
• Cachexia as a consequence of chronic illness
• Obesity and related co-morbidities
• Chronic kidney disease, diabetic kidney disease, and polycystic kidney disease
• Vascular disease

Specific areas of interest include:

• Metabolic treatments of heart failure (HFrEF, HFpEF)
• Novel therapies that target insulin sensitivity in type 2 diabetes
• Addressing obesity and eating disorders to induce and sustain weight loss
• New mechanisms and pathways for the treatment of diabetic nephropathy, chronic kidney disease or polycystic kidney disease
• Novel approaches to target vascular dysfunction

Not actively seeking partnering opportunities in:

• Anti-arrhythmics
• Stable angina treatments

Pfizer Oncology strives to advance the frontiers of cancer biology and to translate this knowledge into high-impact medicines for cancer patients. Our core areas of interest include: Tumor Cell Biology; Precision Medicine; Tumor Targeted Therapeutics; and Immuno-Oncology. In addition, our Integrative Biotechnology Group supports novel target identification and validation through functional genomics, proteomics, and other “omic” approaches.

We are interested in establishing alliances to develop therapeutics, expand disease biology understanding, and identify biomarkers that impact:

• Breast, prostate, lung, bladder, colorectal, renal, melanoma and hematologic cancers

Specific areas of interest include:

• Oncogenic drivers and signaling pathways
• Epigenetics
• Hormone signaling
• Synthetic lethality
• Selective protein degraders
• Transcriptional regulators
• Immune modulators
• Immune cell engagers
• Precision medicine
• Functional genomics
• Liquid biopsy and imaging technologies
• In vivo cell reprogramming

Immuno-Oncology

The clinical successes reported with cancer immunotherapy are reshaping the field of oncology. Pfizer is significantly advancing activity in this area by partnering to

develop cutting edge science beyond the current mainstream immune checkpoints. The IO programs at Pfizer uniquely leverage a combination of our scientific and clinical strength in immunobiology, as well as our historical expertise in developing first-in-class cancer therapies.

Pfizer’s efforts in IO include external collaborative alliances with leading academic medical centers and visionary biotech firms. Our IO efforts are driven primarily by the Cancer Immunology Discovery Unit (CID) within our La Jolla, CA-based laboratory site. Leveraging its strength in biotherapeutics, along with core expertise in immunobiology, CID has a strong record of converting validated targets into novel protein-based therapeutics and advancing molecular and cell-based IO treatments. We would like to partner in the IO space on pre-clinical and clinical-stage immunomodulatory opportunities, with an emphasis on those agents that directly engage or impact T-cell and other tumor-infiltrating immune cell populations.

We are interested in establishing alliances to develop and access:

• Novel Targets for Overcoming Tumor-associated Immune Resistance
  • Targets that impact the immune response to cancer cells; innate immune activation; and immuno-suppression
• Platform Technologies
  • Mechanisms, biomarkers, and screening approaches to identify and accelerate the most promising combination therapies
  • New modalities to promote immune responses: Bi-specific and Tri-specific antibody/cytokine platforms, nanoparticles, or novel T cell receptors (TCRs)
  • Identification of new immune-modulating targets
  • Monitoring of biomarkers of immune-responsiveness and immune-suppression within tumors
  • Novel animal models that recapitulate more faithfully human tumor-immune system interactions

Not actively seeking partnering opportunities in:

• Antisense/siRNA/shRNA therapeutics
• Reformulated cytotoxic agents

With the vision to be a leader in the development of therapeutic solutions for Rare Diseases, we have focused our business development strategy to align with the Category’s objective to identify and prioritize collaborations and partnerships to advance therapies for rare diseases where there remains high unmet need. Pfizer has adopted an innovative and collaborative approach to the development of new medicines for patients with rare diseases. We have a track record of creating innovative strategic partnerships with academic institutions, patient advocacy groups, and commercial enterprises to accelerate the development of novel therapeutics across a wide spectrum of rare diseases. Our expertise in small and large molecule therapeutics, and genetic therapies has resulted in a broad pipeline of potentially transformative medicines across four primary therapeutic areas, namely rare hematology, neurology, renal, cardiology and metabolic diseases. Therefore, we are seeking new business opportunities that span these disease indications and are not limited by molecule type.

Pfizer is interested in partnering to develop therapeutics, expanding our understanding of disease biology, and identifying biomarkers that can help us impact:

• Rare renal and cardiac diseases
• Rare endocrinology & metabolic diseases
• Rare neurologic diseases
• Rare hematologic diseases
• Genetic-based approaches (e.g., gene therapy and gene editing) in the above disease areas

Specific areas of interest include:

• Gene therapy-, gene editing-, and mRNA-based therapies including methods to minimize host immune responses and afford redosing with viral vectors
• Oral small molecule- and biologics-based approaches
• Modifiers of expanded repeat disorders
• Pharmacologic chaperones and other modifiers of protein trafficking, misfolding, or degradation that could be applied to multiple diseases

Not actively seeking partnering opportunities in:

• Dermatology
• Rare oncology
• Ex-vivo gene therapies

Vaccines are one of the greatest public health advancements of all time, resulting in the control, elimination, or near-elimination of numerous infectious diseases that were once pervasive and often fatal. Pfizer has a rich history in vaccine research and development. Over the years, we’ve played a pivotal role in eliminating or nearly eliminating deadly infectious diseases like smallpox and polio globally. We have designed novel vaccines based on new delivery systems and technologies that have resulted in vaccines to prevent bacterial infections, like those caused by S. pneumoniae and N. meningitidis.

Today, more people are benefiting from safe and efficacious vaccines to prevent infectious diseases than ever before, and vaccines provide essential health benefits at all ages, from maternal and infant populations to seniors. However, our work is not done given the many infectious diseases with high unmet medical need as well as the existence of a growing number of diseases which are potentially vaccine- preventable.

It is an exciting time in vaccine research and development, as scientific discoveries, technological advancements and regulatory paradigms are paving the way for novel vaccines. While Pfizer’s Vaccine Research and Development scientists continue to extend our leadership position in pneumococcal and meningococcal disease prevention, they are also working on vaccines against other major infectious diseases while striving to bring the benefits of vaccines into previously unexplored areas. We are at the forefront to usher in a new era of vaccine innovation, to prevent serious infectious diseases that span our life span, protecting infants through maternal immunization and infant immunization through to older adults.

The approval of the first mRNA-based COVID-19 vaccines was a scientific turning point, establishing mRNA as a versatile, flexible technology. The focus and drive Pfizer exhibited in developing our COVID-19 vaccine in partnership with BioNTech produced a wealth of scientific knowledge in just one year.

Pfizer’s next wave of mRNA scientific innovation is expanding in the infectious disease arena with development programs in influenza and shingles, and we are also exploring the application of mRNA technology in other areas, including in rare genetic diseases. Our intention is to evaluate opportunities where the scientific rationale for using mRNA technology along with Pfizer’s expertise in disease is strongest, and where the potential impact on patients could be the greatest.

Pfizer Vaccines is interested in partnering opportunities in Vaccines R&D:

• Infectious disease vaccines that address a high unmet medical need and represent a breakthrough vs. standard of care
• Focus on bacterial and viral vaccines

Specific areas of interest in Vaccine Research include:

• Research tools, reagents, and materials to aid in vaccine discovery
• Novel viral and bacterial antigens (peptides, proteins, DNA, RNA, glycoconjugates) and expression systems
• Immunomodulators, adjuvants, delivery platforms, and vector systems to enhance vaccine immune responses
• Needle-free alternative delivery methods and devices

Broad platform technologies for application across multiple programs

Our focus is to implement innovative diagnostic solutions to enable precision medicine, including, but not limited to, companion and complementary diagnostic testing.

Companion diagnostics are essential for regulatory approval and use of certain precision medicines. These tests are generally co-developed and submitted for regulatory approvals in tandem with drug candidates and included in drug labels, subject to regulatory approval.

Complementary diagnostics are useful in identifying a population that may respond particularly well to a potential treatment, in identifying an underdiagnosed condition as well as diagnosis of various disease states. These tests are not considered essential to prescribing an approved drug and are not included in drug labels.

Pfizer has a diverse pharmaceutical portfolio, and we are interested in a wide range of diagnostic technologies, including companion diagnostics and complementary diagnostics. Relevant diagnostics technologies include, but are not limited to, the following:

• Near-patient Point-of-Care technologies
• Next Generation Sequencing technologies that can use multiple specimen types, including tissue and blood
• Circulating tumor cells
• Circulating cell-free nucleic acids, including potential early cancer detection
• Antigen receptor sequencing
• Neutralizing antibody assays
• Covid and other infectious disease testing platforms

The above would ideally be paired with capabilities and footprint for distribution in global markets, regulatory and reimbursement strategies, and commercialization capabilities.

Pfizer’s Drug Safety R&D scientists develop and apply skills, experience, and cutting-edge tools for quantitative assessment of nonclinical safety and risk management of targets, therapeutic candidates (drugs, vaccine candidates), and marketed products across the research, discovery, development, and commercial phases of drug development. We seek to enrich our capabilities for target and therapeutic candidate safety assessment along with mechanistic understanding of toxicity findings to allow development of an efficient risk management strategy using evidence-based translation of findings between animals and humans.

Specifically, our focus areas include:

Probabilistic screening approaches, mechanistic science to understand safety risks and discovery-development of translatable biomarkers related to target organ toxicity, such as:

• Cardiovascular and vascular injury
• Neuropathology biomarkers (central and peripheral)
• Liver injury, in particular immune-mediated drug-induced liver injury (DILI) and transporters
• Immunosafety concerns including both immunosuppression and immunostimulation, such as hypersensitivity, autoimmunity, complement activation and cytokine release
• Kidney toxicity – glomerular and tubular
• Ocular toxicity – retina and cornea
• Bone marrow toxicity—hematopoietic and myelopoietic (in vitro assay)
• Gastrointestinal toxicity—characterization, mechanistic and translational relevance

Advancing regulatory science using drug development tools (computational, QSAR, microphysiological systems, etc.) to support all therapeutic areas for mono- and combination-therapy approaches (interpretation and translatability

• Novel data insights and applications of Artificial Intelligence (AI) to predict, understand and improve safety assessment
• Systems toxicology approaches using genetic and multi-omics data sets to allow prediction of adverse events and develop a patient risk stratification strategy
• High-resolution screening methodologies (single cell transcriptomics, nanoproteomics), single parameter and multiplex digital image analysis and omics approaches to discover, develop and qualify multi-parametric biomarkers for clinical safety monitoring
• Comparative systems analysis to model responses between animals and humans
• Physiologically-relevant complex in vitro models (e.g., MPS/organ-chips) to de-risk multiple organ toxicity concerns

Biotherapeutics, nanoparticle drug and emerging modalities associated safety issues and mitigation strategies

• Mechanistic and quantitative approaches to understand safety of novel modalities such as gene therapy, gene editing, and protein degrader
• Assays to assess safety of novel biotherapeutics (e.g., bispecifics) and gene therapy for humans
• Anti-Drug Antibodies (ADA) related with polymer-based nanoparticle formulation
• Nanoparticle-specific toxicities and target tissues/organs

Pfizer is committed to leading in this space by bringing together the foremost expertise in gene therapy vector design and development with in-house knowledge of disease biology and manufacturing capabilities. We currently have 3 industry-leading phase 3 clinical gene therapy programs and have invested over $800M to expand our AAV manufacturing capacity. We have entered into multiple gene therapy collaborations, each of which is an important part of our continuing effort to build our gene therapy programs and capabilities. We see gene therapy as a key pillar of our Rare Disease strategy. In addition, we are interested in the application of gene therapy to select central nervous system (CNS), neuromuscular,heart, renal, hematology and metabolic diseases. We are also seeking tissue-selective and tunable expression promoter technologies, as well as vector analytics and immune surveillance approaches, and in-vivo gene editing technologies.

We are interested in partnering to develop and access:

• Rare Neurologic Diseases
  • Huntington’s Disease
  • Genetic Parkinson’s Disease
  • ALS/FTLD
  • Dominant Inherited Alzheimer’s Disease
• Muscular Dystrophies
• Rare Cardiac Diseases
• Sickle Cell Disease
• Rare Metabolic Disease
• Rare Renal Diseases
• Lysosomal Storage Diseases
• Novel AAV vectors and LNPs with strong tissue-specific tropism (CNS, muscle, heart kidney and liver) with favorable transduction/expression
• Promoter or gene regulation technology to ensure regulated and sustained tissue-specific gene expression
• Vector analytics to identify viruses with superior bioactivity
• AAV immunology expertise to test/challenge existing hypotheses and develop more robust gene therapy products

• Biologics Product & Process Development
• Biotherapeutics Development
• Medicine Design
• Small Molecule Product & Process Development

We are focused on Precision Medicine as an approach to discovering and developing potential treatments that can deliver superior outcomes for patients, by integrating clinical and molecular data to understand the biological basis of disease, the pharmacology of our drug candidates and the appropriate patient population to treat. Precision medicine efforts have the potential to lead to better matching of drug targets with selected patient populations that may experience clinical benefit.

We are interested in establishing collaborations to develop and access:

Patient cohorts

• Large-scale datasets with high quality longitudinal clinical (e.g., electronic medical record)
• Molecular, imaging and other phenotypic data appropriately consented, preferably with broadly consented biospecimens (e.g., whole blood serum/plasma, saliva, tissue, PBMCs, stool, etc.)
• Cohorts with the potential to recall patients based on genotype or phenotypefor follow up studies

Systems Biology/Pharmacology

• Databases with high quality data on treatment and disease outcomes associated with genetic, as well as molecular (metabolomic, proteomic transcriptomic, epigenetic, clinical chemistry markers) or functional measures, in particular with associated imaging data
• Databases of searchable expression quantitative trait loci (eQTLs), protein quantitative trail loci (pQTLs) across tissues
• Disease biology guided combination therapy design platforms
• Systems biology approaches and proven in silico tools to evaluate pharmacological perturbation and to elucidate mechanisms of in vivo toxicity
• Mining of data for correlation and understanding of causality

Breakthrough diagnostic technologies that are highly quantitative, require minimal specimen/ tissue, can offer quick turnaround time and can be multiplexed. This will include but is not limited to:

• Near-patient Point-of-Care technologies
• Next Generation Sequencing technologies that can use multiple specimen matrices, including tissue and biofluids
• Circulating tumor cells
• Circulating cell-free nucleic acids
• Antigen receptor sequencing
• The above would ideally be paired with capabilities and footprint for distribution in global markets, regulatory and reimbursement strategies, and commercialization capabilities

In vivo imaging technologies (including MRI, PET, CT, optical imaging technologies, imaging agents, genetically encoded tags, ultrasound, etc.) with particular interest in

• Imaging agents for small and large molecule compound distribution studies
• Imaging agents monitoring physiology mechanisms and disease
• Analytical tools and technologies

Biospecimen Analysis

• Circulating tumor cell and cell free nucleic acid quantification and analysis
• High dimensional single cell analysis platforms
• High dimensional IHC/IF for tissue digital image analyses (cancer, safety)
• Advanced ADME-related genotyping
• Extracellular vesicle, exosome analysis
• 3D cell models for safety and efficacy assessment that ideally incorporate genetic diversity
• Skin tape strip, sebum analysis
• High dimensional flow cytometry
• Emerging “omic” analysis (e.g., phosphoproteome, autoantibody profiling, microbiome in addition to proteomics, metabolomics)

Physiological Biomarkers

• Technologies that have the potential to add enhanced precision to pre-clinical studies
• EEG-based biomarkers

Induced pluripotent stem cell (iPSC) resources and technologies to generate iPSCs that may be used to enable Precision Medicine strategies

• Validated cell differentiation protocols
• PSCs derived from sub populations with specific genotypic/phenotypic data
• Technology that can create iPSCs in a rapid and reproducible fashion without insertional approaches

Biospecimen collection/stabilization technologies:

• Novel sample collection approaches that allow frequent (at home) sample collection with appropriate stabilization (e.g., dried blood spots, swabs)

Remote Patient wearable technologies:

• Novel actigraphy and other wearables that allow frequent at home collection of data regarding relevant physiological states or biomarkers

Advanced computational biology approaches/platforms:

• Integration of high-dimensional data across various platforms in combination with traditional clinical readouts for the predictive modeling of patient response or disease progression
• AI approaches to gaining disease insight, target selection and/or patient populations likely to respond to potential treatment
• Microbiome, including virome characterization

Pfizer is interested in partnering for the advancement of RNA therapeutics and the development of the next generation of RNA medicines

Novel target concepts and therapeutic strategies amenable to RNA based approaches (mRNA, circular RNA, gene editing), in the following areas of interest:

• Cellular reprogramming:
  • Cellular reprogramming in cancer (CRC, Lung, Breast, Prostate, Renal), metabolic, autoimmune disease or fibrosis (e.g. transcription factors). Prioritized lineages include:
    • Myeloid cells (DC, macrophages, monocytes)
    • T cells (induction of Tregs); CAR-Tregs or Treg reprogramming; T cell exhaustion; tolerance
    • Adipocytes, muscle cells, endothelial cells
  • Tunable cytokine/interleukin expression for immune cell modulation in cancer
  • Reprogramming of Myofibroblasts in liver and lung fibrosis
• Infectious Disease Vaccines
  • Protective cell mediated response to bacterial or viral infections
  • Emerging virus threats
  • Bacterial pathogens
• Chronic or Rare Kidney Disease (Focal Segmental Glomerulosclerosis, IgA Nephropathy, Alport Syndrome, or Autosomal Dominant Polycystic Kidney Disease)
• Rare Liver Diseases and Rare Neuromuscular Diseases
• Repeat Expansion Diseases (e.g. Huntington’s disease, Friedreich’s ataxia, ALS, myotonic dystrophy)
• Preference given to targets not amenable to small or large molecule intervention

Technologies and Enabling Infrastructure:

• Gene correction/replacement
• Epigenetic editing
• Delivery technology, including tissue targeting for liver, lung, kidney, immune cell subsets, central nervous system, muscle
• Non-viral delivery for RNA and gene editing
• RNA engineering technologies (e.g. UTRs, IRES, circular RNA, chemical modifications, stability)
• Regulatable gene expression
• Next-gen gene editing

Not actively seeking partnership opportunities in:

• RNA vaccine strategies for Flu, COVID-19, RSV
• Non-coding RNA targets and modalities

Target Sciences (TS) is a genomics partner line with expertise in Human Genetics, Functional Genomics, Computational Biology, and Diagnostics. TS is focused on Pfizer R&D in diagnostics development as well as target discovery and validation of first in class targets with compelling human-based confidence in rationale.

We are interested in establishing alliances to develop and access:

• Highly characterized patient cohorts for genetic studies in diseases of interest to Pfizer
  • Extreme phenotypes
  • Disease progression
  • Patient sub-types
  • Underrepresented ancestry patient cohorts
  • Specific areas of interest, in addition to Pfizer’s core disease areas, include fibrosis, rare kidney diseases, aging, and senescence
• Population-based Biobanks and high-quality, longitudinal genotype - phenotype data sets, including clinical and molecular data, access to biospecimens, and the potential for patient recall
• Computational Biology approaches to understand disease drivers through the integration of human omics data (e.g. genetics, RNA-seq, proteomics, epigenomics, clinical measures)
• AI/ML approaches for novel target and biomarker discovery, patient stratification, and methods of development for multi-omics data analysis and integration
• Novel in silico or in vitro approaches to translate disease associated genetic loci into causal genes and therapeutic hypotheses
• Functional Genomics technologies to accelerate target discovery in disease-relevant biological systems
• Breakthrough diagnostic technologies, including liquid biopsy testing and NGS panels in oncology, and near-patient rapid diagnostics testing in infectious diseases

DNA damage and replication stress play a major role in disease and are a hallmark of cancer. To maintain genome integrity and support normal functions, cells have evolved an intricate network of DNA damage repair and cell-cycle checkpoint pathways, collectively known as the DNA Damage Response (DDR). DDR processes are consistently altered in cancer and loss of genome integrity plays a causal role in cancer development. However, this unique tumor biology and DDR deficiencies can be leveraged therapeutically to effectively kill cancer cells while sparing normal tissues. Pharmacological control of DDR processes might be used to block tumor growth directly by hindering cell division and induce apoptosis, or indirectly by unleashing the immune system against tumor cells. The latter could be achieved by engaging sensing mechanisms of aberrant DNA and RNA by the innate immune system, collectively studied as nucleic acid sensing (NAS). Moreover, in recent years, DDR/NAS processes have been described to play roles in age-related diseases other than cancer, including trinucleotide repeat expansion and auto-inflammatory syndromes. Pfizer scientists are eager to collaborate with leaders in the DDR/NAS space to develop novel, high-impact treatments for patients across therapeutic indications. Gaining control over DDR/NAS processes provides the opportunity to tackle high unmet medical needs from a differentiated angle improving the life of patients.

Pfizer is interested in partnering opportunities in the DNA Damage Response/Nucleic Acid Sensing space to discover novel, life-changing therapies for patients. These approaches can be (m)RNA-, small molecule-, or large molecule-based.

Specific areas of interest include:

• Control of DDR/NAS processes to impact diseases other than cancer, e.g., inhibition of aberrant nucleic acid sensing mechanisms in auto-inflammatory or age-related diseases
• Novel synthetic lethality and chemo-combo opportunities to treat HR-proficient cancer
• Approaches that unleash the immune system against tumors
• Modulation of NAS/innate immune pathways as adjuvants to optimize efficacy and durability of vaccine

Over fifty diseases, most of which primarily affect the nervous system, are caused by expansion of short DNA sequence repeats dispersed throughout the genome. Mechanisms by which expanded repeats drive disease are still emerging and may vary among diseases. However, somatic expansion of repeats in affected tissues appears to be a common pathological driver. Pfizer scientists are interested in establishing collaborations with expert partners in areas that would advance our understanding of mechanisms of DNA repeat expansion and our ability to intervene therapeutically to arrest or prevent pathological expansion and downstream consequences.

Pfizer is exploring partnering opportunities to expand our understanding of mechanisms that govern the length of DNA repeats, and to identify potential therapeutic interventions and modalities.

Specific areas of interest include:

• Novel targets that directly impact the pathogenic repeats
• Molecular mechanisms that modulate pathological repeat length, repeat transcription or translation, or toxic gain-of-function of repeat transcripts
• Biochemical and cell-based assays for DNA mismatch repair or repeat instability
• Translational biomarkers of somatic repeat instability
• Preclinical models of disease, cellular and animal
• Molecular mechanisms that govern microsatellite repeat pathology

Disease areas of high interest include but are not limited to Huntington’s disease (HD), myotonic dystrophy (DM1), Friedreich’s ataxia (FRDA), C9orf72 amyotrophic lateral sclerosis (ALS)

Cellular senescence is a dynamic multistep process induced by various stimuli. These include oncogenic activation, oxidative/genotoxic stress, mitochondrial dysfunction, and chemo/radiotherapy. Senescence is characterized generally by an irreversible cell growth arrest, changes in cellular metabolism, chromatin re-organization (senescence associated heterochromatin foci; SAHF) and induction of a proinflammatory secretome (Senescence Associated Secretory Phenotype; SASP). Transient presence of senescent cells and the SASP limit tissue damage, restore homeostasis and mitigate preneoplastic cell growth. While aspects of cellular senescence and the SASP are physiologically beneficial to preserve organ and tissue homeostasis. Paradoxically, the accumulation and chronic presence of senescent cells can be detrimental.

The persistence of senescent cells and SASPs can drive neoplastic conversion. Further, the accumulation of senescence cells within a tumor can enhance both immune evasion and suppression. Promising therapeutic approaches focusing on either clearance of senescent cells (senolytics) or prevention of their proinflammatory impact (SASP blockade) are in development. In cancer, a “one-two punch” approach in which an initial drug that selectively induces senescence in the tumor cells is combined or quickly followed by a senolytic agent that eradicates the senescent cells, has recently been proposed to potentiate conventional therapies.

Evidence is emerging that the accumulation of senescent cells in organs can be a significant contributing factor in autoimmunity, fibrosis, and subsequent organ dysfunction. Clearance of senescent cells can alleviate fibrotic progression but there are no current interventions available that can efficiently and durably reverse fibrosis. Thus, potential therapeutic approaches that inhibit or reverse fibrosis could come in the form of senomorphics that alter the fibrosis-associated SASP profile or senolytics capable of selectively eliminating senescent myofibroblasts/fibroblasts or mesenchymal cells in the respective tissue.

Immunosenescence is an emerging aspect of senescence, in which both the innate and adaptive arms of the immune system are dysregulated. It manifests by chronic inflammation (inflammaging), autoimmunity, defective responses to vaccines and pathogens, and reduced tissue/organ immune surveillance. Therapies in this area aim toward enhancing or normalizing immune cell functions that could have significant impact in resolution of autoimmunity and potentiation of cancer immunotherapies.

Specific Areas of Interest Include:

• Reduce the survival and/or prevent the induction of therapy induced senescent tumor cells
• Modulate cellular immuno-senescence to attenuate autoimmunity and enhance anti-tumor/vaccine responses
• Therapeutically target senescent cells in fibrosis to enhance immune clearance, induce cell death or drive tissue repair
• Therapeutic approaches include senolytics and senomorphics

We engage with academia and other public bodies in a range of partnerships, some models include:

• Centers for Therapeutic Innovation (CTI)

Our biotech partnerships allow us to help you bring your drug or platform to market, with a focus on:

• Licensing options
• Acquisition

Contacts:

• Robert Bagdorf, Candidate through Commercialization

• Uwe Schoenbeck, Discovery through Pre-Candidate

Our equity investments are active partnerships that seek to identify, support and grow good science from an early stage.

• Pfizer Ventures